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Cell Host Microbe. 2018 Jun 13;23(6):766-774.e5. doi: 10.1016/j.chom.2018.04.013. Epub 2018 May 17.

The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification.

Author information

1
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
2
Department of Cell Physiology and Metabolism, University of Geneva, Geneva 1211, Switzerland.
3
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), Vienna 1030, Austria.
4
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, Vienna 1090, Austria. Electronic address: gsuperti@cemm.oeaw.ac.at.

Abstract

Macrophages represent the first line of immune defense against pathogens, and phagosome acidification is a necessary step in pathogen clearance. Here, we identified the bicarbonate transporter SLC4A7, which is strongly induced upon macrophage differentiation, as critical for phagosome acidification. Loss of SLC4A7 reduced acidification of phagocytosed beads or bacteria and impaired the intracellular microbicidal capacity in human macrophage cell lines. The phenotype was rescued by wild-type SLC4A7, but not by SLC4A7 mutants, affecting transport capacity or cell surface localization. Loss of SLC4A7 resulted in increased cytoplasmic acidification during phagocytosis, suggesting that SLC4A7-mediated, bicarbonate-driven maintenance of cytoplasmic pH is necessary for phagosome acidification. Altogether, we identify SLC4A7 and bicarbonate-driven cytoplasmic pH homeostasis as an important element of phagocytosis and the associated microbicidal functions in macrophages.

KEYWORDS:

CRISPR screen; NBC3; NBCn1; SLC4A7; intracellular bacterial killing; macrophages; phagocytosis; phagosome acidification; solute carrier

PMID:
29779931
PMCID:
PMC6002608
DOI:
10.1016/j.chom.2018.04.013
[Indexed for MEDLINE]
Free PMC Article

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